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Disseminated Rhodococcus equi infection in a kidney transplant patient without initial pulmonary involvement
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Diagnostic Microbiology and Infectious Disease 65 (2009) 427 – 430 www.elsevier.com/locate/diagmicrobio
Case Report
Disseminated Rhodococcus equi infection in a kidney transplant patient without initial pulmonary involvement Janette C. Rahamat-Langendoena,⁎, Matijs van Meursb , Jan G. Zijlstrab , Jerome R. Lo-Ten-Foea a
Department of Medical Microbiology, University Medical Centre Groningen, Groningen University, PO Box 30 001, 3700 RB, Groningen, The Netherlands b Department of Critical Care, University Medical Centre Groningen, Groningen University, PO Box 30 001, 3700 RB Groningen, The Netherlands Received 24 April 2009; accepted 8 August 2009
Abstract Rhodococcus equi is increasingly recognized as an opportunistic pathogen in solid organ transplant recipients. Primary pulmonary involvement is the most common finding. We report a case of a 42-year-old female kidney transplant recipient who developed multiple disseminated abscesses caused by R. equi while on adequate antimicrobial therapy. The patient presented with subcutaneous abscesses in the hip region and mamma and had 2 intracerebral abscesses. There were no clinical and radiologic signs of pulmonary involvement in contrast to most clinical cases described in the literature. R. equi was cultured from all abscesses. The patient died of progressive neurologic complications. Post mortem examination confirmed infection with R. equi and showed microscopic evidence of necrotizing pneumonia. This report shows that R. equi should be considered as a cause of infection in solid organ transplant recipients even without initial clinical and radiologic signs of pulmonary involvement. Despite adequate therapy, the outcome can be fatal. © 2009 Elsevier Inc. All rights reserved. Keywords: Solid organ transplant; Opportunistic infection; Rhodococcus; Abscess
1. Introduction Rhodococcus equi is a well-documented pathogen in veterinary literature causing pneumonia and sepsis in farm animals, especially in horses and cattle. It is an unusual cause of infection in humans and is typically described in immunocompromised patients. The first case of human infection was reported in 1967 when R. equi was cultured from lung specimens of a young man working in a stockyard, who was undergoing treatment with prednisone and 6-mercaptopurine for autoimmune hepatitis (Golub et al., 1967). In the following years, sporadic human infections with R. equi were reported. However, the incidence of R. equi infections has increased markedly, coinciding with the HIV epidemic and the developments in organ transplantation and cancer treatment (Weinstock and Brown, 2002). Clinical manifestations of R. equi infections
⁎ Corresponding author. Tel.: +31-50-36-13480; fax: +31-50-36-33-528. E-mail address: [email protected] (J.C. Rahamat-Langendoen). 0732-8893/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.diagmicrobio.2009.08.004
most frequently involve the lung, although various other sites can be infected. We report a clinical case of disseminated infection with multiple abscesses caused by R. equi in a kidney transplant patient who showed no clinical and radiologic signs of pulmonary involvement.
2. Case report A 42-year-old woman developed end-stage renal failure because of hemolytic uremic syndrome and malignant hypertension in 2001. She underwent kidney transplantation in 2003, 5 years before current presentation. The maintenance immunosuppressive therapy at the time of presentation consisted of mycophenolate mofetil (500 mg bid), tacrolimus (1 mg bid), and prednisolone (7.5 mg once a day). Initially, she presented with a deep subcutaneous abscess in her right hip, which was treated with surgical drainage and antibiotic therapy (imipenem 1000 mg tid and doxycycline 200 mg once a day, for approximately 1 week). R. equi was identified in cultures from drained material from the subcutaneous abscess. Five weeks after this episode, she
428
J.C. Rahamat-Langendoen et al. / Diagnostic Microbiology and Infectious Disease 65 (2009) 427–430
presented herself again with an abscess in her right hip, for which she again underwent surgical drainage. During her stay at the hospital, she developed epileptic seizures. Computed tomogram (CT) and magnetic resonance imaging (MRI) showed 2 brain abscesses that were not accessible to surgery (the size of the abscesses on the CT scan was less than 1 cm) (Figs. 1 and 2). After 2 days, she suddenly became unconscious, with pulseless electrical activity. After resuscitation, she was transferred to the intensive care unit of our hospital for further treatment. Physical examination showed a wound at her right hip and 2 cutaneous abscesses near the right mamma. Laboratory data included an elevated white blood count of 12.8 × 109/L and elevated C-reactive protein of 261 mg/L. Hemoglobin was 5.3 mmol/L; plasma creatinine was slightly elevated (103 μmol/L). Liver function tests were normal. Ultrasound examination of the heart showed no evidence of endocarditis. CT of the thorax showed no abnormalities, especially no lung abscesses. One week after the first MRI, recurrent MRI of the brain showed, besides the 2 abscesses already described, metastatic lesions and signs of meningitis. Cultures of material from the abscesses at the right hip and mamma on routine nonselective media grew salmon-colored mucoid-appearing colonies. Gram stain showed Gram-positive rods, with branching. R. equi was identified by conventional biochemical tests and by API Coryne identification system (BioMérieux, France).These results were confirmed by 16S rDNA sequencing. Antibiotic therapy was changed from meropenem and doxycycline into imipenem and rifampicin
Fig. 2. MRI brain. Abscess in right frontoparietal part of the brain, with surrounding edema. Size of abscess, 12 mm.
(600 mg bid, intravenously) based on new susceptibility data (Table 1). Immunosuppressive therapy was stopped except for corticosteroids. Because the patient continued to have seizures and rifampicin toxicity could not be excluded, rifampicin was changed after 5 days of therapy into moxifloxacin (400 mg once a day). During her stay, she developed multiple blue-gray skin infiltrates suspected to be disseminated infection. Despite adequate antibiotic therapy, the clinical condition further deteriorated, and the patient eventually died of intractable intracranial hypertension and transtentorial brain herniation almost 14 days after admission to our hospital. Permission for autopsy was obtained. Besides the known abscesses at the hip, mamma, and brain, autopsy showed only microscopic signs of necrotizing pneumonia. Infection with R. equi was confirmed biochemically and by 16S rDNA sequencing after culture of post mortem material obtained from all abscesses.
Table 1 Susceptibility pattern R. equi based on Etest
Fig. 1. MRI brain. Abscess visible in left cerebellum (13 mm in size). No midline shift.
Antibiotic agent
MIC (μg/mL)
Imipenem Doxycycline Erythromycin Rifampicin Meropenem Moxifloxacin Vancomycin
0.75 6 N32 0.50 8 0.25 24
J.C. Rahamat-Langendoen et al. / Diagnostic Microbiology and Infectious Disease 65 (2009) 427–430
3. Discussion R. equi (formerly Corynebacterium equi) is a Grampositive, nonmotile, asporogenous, obligate aerobic microorganism. The microscopic morphology varies from coccoid to bacillary, depending on growth conditions and the phase of the growth cycle (Funke and Bernard, 2007). It grows readily on nonselective media and forms smooth to mucoid colonies that may become increasingly pigmented with age, hence, its name “red pigmented coccus”. R. equi is a facultative intracellular pathogen, infecting macrophages in humans, which is thought to be the basis of its pathogenicity and mechanism of antibiotic resistance. Laboratory diagnosis can be difficult because there is a phenotypic resemblance with other, nonpathogenic, coryneform bacteria. Infection is usually acquired through inhalation from infected soil, inoculation into a wound or mucous membrane, or ingestion and passage through the alimentary tract (Weinstock and Brown, 2002). Contact with domesticated animals, such as horses, or their manure may play a role in some cases of infection (Munoz et al., 1998; Perez et al., 2002; Stolk-Engelaar et al., 1995). No such contact was reported by our patient. Well over 100 cases of R. equi infection have been described in the literature, with most infections in either HIV-infected patients or in patients who are otherwise immunocompromised (Kedlaya et al., 2001; Weinstock and Brown, 2002). Infection in immunocompetent patients is very rare. Approximately 10% of R. equi infections occur in organ transplant recipients. To our knowledge, 32 cases of infection with R. equi have been described in solid organ transplants. Most cases occurred in renal transplant patients (19), followed by heart transplant (6) and liver (2) transplant patients and 1 each in pancreas, combined pancreas and renal, bone marrow, and lung transplant patients (Arya et al., 2004; Speck et al., 2008; Tse et al., 2008). The most common clinical manifestation was necrotizing pneumonia, which occurred in 27 of the 32 reported cases (Arya et al., 2004; Perez et al., 2002). Other manifestations included osteomyelitis (3 patients), purulent pericarditis (1 patient), subcutaneous abscesses (4 patients), and brain abscesses (1 patient). Two patients died because of infection, both kidney transplant recipients. Extrapulmonary disease is thought to result either from contiguous or hematogenous dissemination of the pathogen. Most common sites of metastatic infection are brain, bone, and subcutaneous tissue (Meyer and Reboli, 2005). Our patient is indeed remarkable because she developed disseminated abscesses caused by R. equi without any clinical and radiologic sign of pulmonary involvement. However, microscopic examination of the lungs post mortem did show signs of necrotizing pneumonia. This raises the question whether the primary source of infection was the lungs despite the absence of evidence of involvement of the lungs during life. On the other hand, metastatic abscesses originating from the right hip as the primary source of infection cannot be ruled out, although no
429
intracardiac right-left shunting could be visualized by transesophageal echocardiography. Standards for treatment of R. equi infection have not been well established. A combination of antibiotics guided by susceptibility testing is the mainstay of treatment so far. In addition, surgical drainage of cavities or abscesses is frequently necessary. R. equi is usually susceptible in vitro to erythromycin, rifampicin, fluoroquinolones, aminoglycosides, glycopeptides, and imipenem. Isolates are typically resistant to penicillin. Based on in vitro susceptibility data and published case reports, Weinstock and Brown (2002) advised intravenous therapy with 2 or 3 drug regimens that include vancomycin, imipenem, aminoglycosides, ciprofloxacin, rifampin, and/or erythromycin. There is no agreement on the duration of antimicrobial therapy. This depends on the site and extent of infection, underlying immunocompetence of the host, and the clinical response to therapy (Weinstock and Brown, 2002). For immunocompromised patients with involvement of the lung, bone, or central nervous system, it is, however, generally accepted that antibiotic treatment should be given for a minimum of 6 months, with intravenous therapy during the first 2 to 4 weeks. After clinical improvement, oral antimicrobial agents can be substituted and continued until all culture results are negative and patients' symptoms have resolved (Tse et al., 2008; Weinstock and Brown, 2002). Antibiotic resistance among R. equi isolates is rare but has been reported for several antibiotics, including erythromycin and rifampin (Asoh et al., 2003; Hsueh et al., 1998; Nordmann and Ronco, 1992). In our patient, R. equi was found to be resistant to various antibiotics including vancomycin (MIC, 24.0 μg/mL), erythromycin (MIC, N32 μg/mL), and minocycline (MIC, 6 μg/mL). Vancomycin is regarded in animal models as one of the most effective agents in treatment of R. equi infection, next to erythromycin and rifampin (Nordmann and Ronco, 1992). In our patient, R. equi was found to be sensitive to rifampicin (MIC, 0.5 μg/mL), imipenem (MIC, 0.75 μg/mL), and moxifloxacin (MIC, 0.25 μg/mL). Despite in vitro adequate antibiotic therapy, however, our patient died because of intracerebral complications. In general, mortality rates because of R. equi infection range from 20% to 25% among non–HIV-infected immunocompromised patients compared with mortality rates of 50% among HIV-infected patients and around 11% among immunocompetent patients (Kedlaya et al., 2001). The capacity of the bacteria to survive within macrophages may be the reason for the severe and recurrent clinical course of infection with R. equi (Funke and Bernard, 2007). Besides, difficulties in identifying the organism can cause delay in diagnosis, and initial antimicrobial therapy may be inappropriate, resulting in more serious disease. Also, relapses of infection are common. Susceptibility testing should be performed for all R. equi isolates to avoid use of antibiotics to which the isolate has in vitro resistance. Besides combination antibiotic therapy, surgical drainage of large cavities, and abscesses in sites of poor antibiotic penetration
430
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is probably beneficial. In our patient, surgical drainage of the brain abscesses was not possible. This, together with in vitro found antibiotic resistance of R. equi, may have contributed to the fatal outcome. This case report shows that despite the absence of clinical and radiologic signs of pulmonary involvement, R. equi infection should be considered in solid organ transplant recipients. It further emphasizes that infection with R. equi can be fatal even if treated with in vitro effective therapy. Therefore, this opportunistic pathogen should not be overlooked, and the worldwide experience should be shared to develop better treatment strategies. References Arya B, Hussian S, Hariharan S (2004) Rhodococcus equi pneumonia in a renal transplant patient: a case report and review of literature. Clin Transplant 18:748–752. Asoh N, Watanabe H, Fines-Guyon M, Watanabe K, Oishi K, Kositsakulchai W, et al (2003) Emergence of rifampin-resistant Rhodococcus equi with several types of mutations in the rpoB gene among AIDS patients in northern Thailand. J Clin Microbiol 41:2337–2340. Funke G, Bernard KA (2007) Coryneform Gram-positive rods. In: Manual of clinical microbiology. 9th ed. Murray PR, Barron EJ, Jorgensen JH, Landry ML, Pfaller MA, Eds. Washington, DC: ASM Press. Golub B, Falk G, Spink WW (1967) Lung abscess due to Corynebacterium equi. Report of first human infection. Ann Intern Med 66:1174–1177.
Hsueh PR, Hung CC, Teng LJ, Yu MC, Chen YC, Wang HK, et al (1998) Report of invasive Rhodococcus equi infections in Taiwan, with an emphasis on the emergence of multidrug-resistant strains. Clin Infect Dis 27:370–375. Kedlaya I, Ing MB, Wong SS (2001) Rhodococcus equi infections in immunocompetent hosts: case report and review. Clin Infect Dis 32: E39–E46. Meyer DK, Reboli AC (2005) Other coryneform bacteria and Rhodococcus. In: Principles and practice of infectious diseases. 6th ed. Mandell GL, Bennett JE, Dolin R, Eds. New York: Churchill Livingstone, pp. 2472–2474. Munoz P, Burillo A, Palomo J, Rodriguez-Creixems M, Bouza E (1998) Rhodococcus equi infection in transplant recipients: case report and review of the literature. Transplantation 65:449–453. Nordmann P, Ronco E (1992) In-vitro antimicrobial susceptibility of Rhodococcus equi. J Antimicrob Chemother 29:383–393. Perez MG, Vassilev T, Kemmerly SA (2002) Rhodococcus equi infection in transplant recipients: a case of mistaken identity and review of the literature. Transpl Infect Dis 4:52–56. Speck D, Koneth I, Diethelm M, Binet I (2008) A pulmonary mass caused by Rhodococcus equi infection in a renal transplant recipient. Nat Clin Pract Nephrol 4:398–403. Stolk-Engelaar MV, Dompeling EC, Meis JF, Hoogkamp-Korstanje JA (1995) Disseminated abscesses caused by Rhodococcus equi in a patient with chronic lymphocytic leukemia. Clin Infect Dis 20:478–479. Tse KC, Tang SC, Chan TM, Lai KN (2008) Rhodococcus lung abscess complicating kidney transplantation: successful management by combination antibiotic therapy. Transpl Infect Dis 10:44–47. Weinstock DM, Brown AE (2002) Rhodococcus equi: an emerging pathogen. Clin Infect Dis 34:1379–1385.
Diagnostic Microbiology and Infectious Disease 65 (2009) 427 – 430 www.elsevier.com/locate/diagmicrobio
Case Report
Disseminated Rhodococcus equi infection in a kidney transplant patient without initial pulmonary involvement Janette C. Rahamat-Langendoena,⁎, Matijs van Meursb , Jan G. Zijlstrab , Jerome R. Lo-Ten-Foea a
Department of Medical Microbiology, University Medical Centre Groningen, Groningen University, PO Box 30 001, 3700 RB, Groningen, The Netherlands b Department of Critical Care, University Medical Centre Groningen, Groningen University, PO Box 30 001, 3700 RB Groningen, The Netherlands Received 24 April 2009; accepted 8 August 2009
Abstract Rhodococcus equi is increasingly recognized as an opportunistic pathogen in solid organ transplant recipients. Primary pulmonary involvement is the most common finding. We report a case of a 42-year-old female kidney transplant recipient who developed multiple disseminated abscesses caused by R. equi while on adequate antimicrobial therapy. The patient presented with subcutaneous abscesses in the hip region and mamma and had 2 intracerebral abscesses. There were no clinical and radiologic signs of pulmonary involvement in contrast to most clinical cases described in the literature. R. equi was cultured from all abscesses. The patient died of progressive neurologic complications. Post mortem examination confirmed infection with R. equi and showed microscopic evidence of necrotizing pneumonia. This report shows that R. equi should be considered as a cause of infection in solid organ transplant recipients even without initial clinical and radiologic signs of pulmonary involvement. Despite adequate therapy, the outcome can be fatal. © 2009 Elsevier Inc. All rights reserved. Keywords: Solid organ transplant; Opportunistic infection; Rhodococcus; Abscess
1. Introduction Rhodococcus equi is a well-documented pathogen in veterinary literature causing pneumonia and sepsis in farm animals, especially in horses and cattle. It is an unusual cause of infection in humans and is typically described in immunocompromised patients. The first case of human infection was reported in 1967 when R. equi was cultured from lung specimens of a young man working in a stockyard, who was undergoing treatment with prednisone and 6-mercaptopurine for autoimmune hepatitis (Golub et al., 1967). In the following years, sporadic human infections with R. equi were reported. However, the incidence of R. equi infections has increased markedly, coinciding with the HIV epidemic and the developments in organ transplantation and cancer treatment (Weinstock and Brown, 2002). Clinical manifestations of R. equi infections
⁎ Corresponding author. Tel.: +31-50-36-13480; fax: +31-50-36-33-528. E-mail address: [email protected] (J.C. Rahamat-Langendoen). 0732-8893/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.diagmicrobio.2009.08.004
most frequently involve the lung, although various other sites can be infected. We report a clinical case of disseminated infection with multiple abscesses caused by R. equi in a kidney transplant patient who showed no clinical and radiologic signs of pulmonary involvement.
2. Case report A 42-year-old woman developed end-stage renal failure because of hemolytic uremic syndrome and malignant hypertension in 2001. She underwent kidney transplantation in 2003, 5 years before current presentation. The maintenance immunosuppressive therapy at the time of presentation consisted of mycophenolate mofetil (500 mg bid), tacrolimus (1 mg bid), and prednisolone (7.5 mg once a day). Initially, she presented with a deep subcutaneous abscess in her right hip, which was treated with surgical drainage and antibiotic therapy (imipenem 1000 mg tid and doxycycline 200 mg once a day, for approximately 1 week). R. equi was identified in cultures from drained material from the subcutaneous abscess. Five weeks after this episode, she
428
J.C. Rahamat-Langendoen et al. / Diagnostic Microbiology and Infectious Disease 65 (2009) 427–430
presented herself again with an abscess in her right hip, for which she again underwent surgical drainage. During her stay at the hospital, she developed epileptic seizures. Computed tomogram (CT) and magnetic resonance imaging (MRI) showed 2 brain abscesses that were not accessible to surgery (the size of the abscesses on the CT scan was less than 1 cm) (Figs. 1 and 2). After 2 days, she suddenly became unconscious, with pulseless electrical activity. After resuscitation, she was transferred to the intensive care unit of our hospital for further treatment. Physical examination showed a wound at her right hip and 2 cutaneous abscesses near the right mamma. Laboratory data included an elevated white blood count of 12.8 × 109/L and elevated C-reactive protein of 261 mg/L. Hemoglobin was 5.3 mmol/L; plasma creatinine was slightly elevated (103 μmol/L). Liver function tests were normal. Ultrasound examination of the heart showed no evidence of endocarditis. CT of the thorax showed no abnormalities, especially no lung abscesses. One week after the first MRI, recurrent MRI of the brain showed, besides the 2 abscesses already described, metastatic lesions and signs of meningitis. Cultures of material from the abscesses at the right hip and mamma on routine nonselective media grew salmon-colored mucoid-appearing colonies. Gram stain showed Gram-positive rods, with branching. R. equi was identified by conventional biochemical tests and by API Coryne identification system (BioMérieux, France).These results were confirmed by 16S rDNA sequencing. Antibiotic therapy was changed from meropenem and doxycycline into imipenem and rifampicin
Fig. 2. MRI brain. Abscess in right frontoparietal part of the brain, with surrounding edema. Size of abscess, 12 mm.
(600 mg bid, intravenously) based on new susceptibility data (Table 1). Immunosuppressive therapy was stopped except for corticosteroids. Because the patient continued to have seizures and rifampicin toxicity could not be excluded, rifampicin was changed after 5 days of therapy into moxifloxacin (400 mg once a day). During her stay, she developed multiple blue-gray skin infiltrates suspected to be disseminated infection. Despite adequate antibiotic therapy, the clinical condition further deteriorated, and the patient eventually died of intractable intracranial hypertension and transtentorial brain herniation almost 14 days after admission to our hospital. Permission for autopsy was obtained. Besides the known abscesses at the hip, mamma, and brain, autopsy showed only microscopic signs of necrotizing pneumonia. Infection with R. equi was confirmed biochemically and by 16S rDNA sequencing after culture of post mortem material obtained from all abscesses.
Table 1 Susceptibility pattern R. equi based on Etest
Fig. 1. MRI brain. Abscess visible in left cerebellum (13 mm in size). No midline shift.
Antibiotic agent
MIC (μg/mL)
Imipenem Doxycycline Erythromycin Rifampicin Meropenem Moxifloxacin Vancomycin
0.75 6 N32 0.50 8 0.25 24
J.C. Rahamat-Langendoen et al. / Diagnostic Microbiology and Infectious Disease 65 (2009) 427–430
3. Discussion R. equi (formerly Corynebacterium equi) is a Grampositive, nonmotile, asporogenous, obligate aerobic microorganism. The microscopic morphology varies from coccoid to bacillary, depending on growth conditions and the phase of the growth cycle (Funke and Bernard, 2007). It grows readily on nonselective media and forms smooth to mucoid colonies that may become increasingly pigmented with age, hence, its name “red pigmented coccus”. R. equi is a facultative intracellular pathogen, infecting macrophages in humans, which is thought to be the basis of its pathogenicity and mechanism of antibiotic resistance. Laboratory diagnosis can be difficult because there is a phenotypic resemblance with other, nonpathogenic, coryneform bacteria. Infection is usually acquired through inhalation from infected soil, inoculation into a wound or mucous membrane, or ingestion and passage through the alimentary tract (Weinstock and Brown, 2002). Contact with domesticated animals, such as horses, or their manure may play a role in some cases of infection (Munoz et al., 1998; Perez et al., 2002; Stolk-Engelaar et al., 1995). No such contact was reported by our patient. Well over 100 cases of R. equi infection have been described in the literature, with most infections in either HIV-infected patients or in patients who are otherwise immunocompromised (Kedlaya et al., 2001; Weinstock and Brown, 2002). Infection in immunocompetent patients is very rare. Approximately 10% of R. equi infections occur in organ transplant recipients. To our knowledge, 32 cases of infection with R. equi have been described in solid organ transplants. Most cases occurred in renal transplant patients (19), followed by heart transplant (6) and liver (2) transplant patients and 1 each in pancreas, combined pancreas and renal, bone marrow, and lung transplant patients (Arya et al., 2004; Speck et al., 2008; Tse et al., 2008). The most common clinical manifestation was necrotizing pneumonia, which occurred in 27 of the 32 reported cases (Arya et al., 2004; Perez et al., 2002). Other manifestations included osteomyelitis (3 patients), purulent pericarditis (1 patient), subcutaneous abscesses (4 patients), and brain abscesses (1 patient). Two patients died because of infection, both kidney transplant recipients. Extrapulmonary disease is thought to result either from contiguous or hematogenous dissemination of the pathogen. Most common sites of metastatic infection are brain, bone, and subcutaneous tissue (Meyer and Reboli, 2005). Our patient is indeed remarkable because she developed disseminated abscesses caused by R. equi without any clinical and radiologic sign of pulmonary involvement. However, microscopic examination of the lungs post mortem did show signs of necrotizing pneumonia. This raises the question whether the primary source of infection was the lungs despite the absence of evidence of involvement of the lungs during life. On the other hand, metastatic abscesses originating from the right hip as the primary source of infection cannot be ruled out, although no
429
intracardiac right-left shunting could be visualized by transesophageal echocardiography. Standards for treatment of R. equi infection have not been well established. A combination of antibiotics guided by susceptibility testing is the mainstay of treatment so far. In addition, surgical drainage of cavities or abscesses is frequently necessary. R. equi is usually susceptible in vitro to erythromycin, rifampicin, fluoroquinolones, aminoglycosides, glycopeptides, and imipenem. Isolates are typically resistant to penicillin. Based on in vitro susceptibility data and published case reports, Weinstock and Brown (2002) advised intravenous therapy with 2 or 3 drug regimens that include vancomycin, imipenem, aminoglycosides, ciprofloxacin, rifampin, and/or erythromycin. There is no agreement on the duration of antimicrobial therapy. This depends on the site and extent of infection, underlying immunocompetence of the host, and the clinical response to therapy (Weinstock and Brown, 2002). For immunocompromised patients with involvement of the lung, bone, or central nervous system, it is, however, generally accepted that antibiotic treatment should be given for a minimum of 6 months, with intravenous therapy during the first 2 to 4 weeks. After clinical improvement, oral antimicrobial agents can be substituted and continued until all culture results are negative and patients' symptoms have resolved (Tse et al., 2008; Weinstock and Brown, 2002). Antibiotic resistance among R. equi isolates is rare but has been reported for several antibiotics, including erythromycin and rifampin (Asoh et al., 2003; Hsueh et al., 1998; Nordmann and Ronco, 1992). In our patient, R. equi was found to be resistant to various antibiotics including vancomycin (MIC, 24.0 μg/mL), erythromycin (MIC, N32 μg/mL), and minocycline (MIC, 6 μg/mL). Vancomycin is regarded in animal models as one of the most effective agents in treatment of R. equi infection, next to erythromycin and rifampin (Nordmann and Ronco, 1992). In our patient, R. equi was found to be sensitive to rifampicin (MIC, 0.5 μg/mL), imipenem (MIC, 0.75 μg/mL), and moxifloxacin (MIC, 0.25 μg/mL). Despite in vitro adequate antibiotic therapy, however, our patient died because of intracerebral complications. In general, mortality rates because of R. equi infection range from 20% to 25% among non–HIV-infected immunocompromised patients compared with mortality rates of 50% among HIV-infected patients and around 11% among immunocompetent patients (Kedlaya et al., 2001). The capacity of the bacteria to survive within macrophages may be the reason for the severe and recurrent clinical course of infection with R. equi (Funke and Bernard, 2007). Besides, difficulties in identifying the organism can cause delay in diagnosis, and initial antimicrobial therapy may be inappropriate, resulting in more serious disease. Also, relapses of infection are common. Susceptibility testing should be performed for all R. equi isolates to avoid use of antibiotics to which the isolate has in vitro resistance. Besides combination antibiotic therapy, surgical drainage of large cavities, and abscesses in sites of poor antibiotic penetration
430
J.C. Rahamat-Langendoen et al. / Diagnostic Microbiology and Infectious Disease 65 (2009) 427–430
is probably beneficial. In our patient, surgical drainage of the brain abscesses was not possible. This, together with in vitro found antibiotic resistance of R. equi, may have contributed to the fatal outcome. This case report shows that despite the absence of clinical and radiologic signs of pulmonary involvement, R. equi infection should be considered in solid organ transplant recipients. It further emphasizes that infection with R. equi can be fatal even if treated with in vitro effective therapy. Therefore, this opportunistic pathogen should not be overlooked, and the worldwide experience should be shared to develop better treatment strategies. References Arya B, Hussian S, Hariharan S (2004) Rhodococcus equi pneumonia in a renal transplant patient: a case report and review of literature. Clin Transplant 18:748–752. Asoh N, Watanabe H, Fines-Guyon M, Watanabe K, Oishi K, Kositsakulchai W, et al (2003) Emergence of rifampin-resistant Rhodococcus equi with several types of mutations in the rpoB gene among AIDS patients in northern Thailand. J Clin Microbiol 41:2337–2340. Funke G, Bernard KA (2007) Coryneform Gram-positive rods. In: Manual of clinical microbiology. 9th ed. Murray PR, Barron EJ, Jorgensen JH, Landry ML, Pfaller MA, Eds. Washington, DC: ASM Press. Golub B, Falk G, Spink WW (1967) Lung abscess due to Corynebacterium equi. Report of first human infection. Ann Intern Med 66:1174–1177.
Hsueh PR, Hung CC, Teng LJ, Yu MC, Chen YC, Wang HK, et al (1998) Report of invasive Rhodococcus equi infections in Taiwan, with an emphasis on the emergence of multidrug-resistant strains. Clin Infect Dis 27:370–375. Kedlaya I, Ing MB, Wong SS (2001) Rhodococcus equi infections in immunocompetent hosts: case report and review. Clin Infect Dis 32: E39–E46. Meyer DK, Reboli AC (2005) Other coryneform bacteria and Rhodococcus. In: Principles and practice of infectious diseases. 6th ed. Mandell GL, Bennett JE, Dolin R, Eds. New York: Churchill Livingstone, pp. 2472–2474. Munoz P, Burillo A, Palomo J, Rodriguez-Creixems M, Bouza E (1998) Rhodococcus equi infection in transplant recipients: case report and review of the literature. Transplantation 65:449–453. Nordmann P, Ronco E (1992) In-vitro antimicrobial susceptibility of Rhodococcus equi. J Antimicrob Chemother 29:383–393. Perez MG, Vassilev T, Kemmerly SA (2002) Rhodococcus equi infection in transplant recipients: a case of mistaken identity and review of the literature. Transpl Infect Dis 4:52–56. Speck D, Koneth I, Diethelm M, Binet I (2008) A pulmonary mass caused by Rhodococcus equi infection in a renal transplant recipient. Nat Clin Pract Nephrol 4:398–403. Stolk-Engelaar MV, Dompeling EC, Meis JF, Hoogkamp-Korstanje JA (1995) Disseminated abscesses caused by Rhodococcus equi in a patient with chronic lymphocytic leukemia. Clin Infect Dis 20:478–479. Tse KC, Tang SC, Chan TM, Lai KN (2008) Rhodococcus lung abscess complicating kidney transplantation: successful management by combination antibiotic therapy. Transpl Infect Dis 10:44–47. Weinstock DM, Brown AE (2002) Rhodococcus equi: an emerging pathogen. Clin Infect Dis 34:1379–1385.